The overall objective of this investigation is to gain further insight into the biochemical mechanism by which estrogenic hormones promote growth of hormone-dependent tissues and tumors. Having established that the nuclear estradiol-receptor complex is derived from an initial extranuclear complex by the hormone-induced conversion of the receptor protein (estrophilin) to an activated form that can bind in the nucleus, investigative attention will be centered on: (1) the chemical structure of the receptor protein, (2) the molecular basis of receptor transformation, and (3) the nature of the nuclear acceptor site with which the transformed complex interacts in the target cell nucleus. The principal effort will be devoted to the isolation of tangible quantities of the pure nuclear and cytosol forms of estrophilin from human uterus for determination of composition, structure and biochemical properties. We shall utilize the purification procedure developed for the stabilized forms of calf uterine estrophilin. Antibodies to each protein will be prepared and used for immunochemical evaluation of tissue and species specificity of estrophilin structure and of similarities and differences between various receptor forms, as well as for the preparation of immunochemical affinity columns that may provide rapid and efficient purification of the receptor protein. Interaction with purified uterine nuclei and with isolated chromatin will be compared for complexed and steroid-free transformed estrophilin, using the effect on RNA synthesis as a marker of biologic activity.